Riboflavin commercially available today is produced partly synthetically and partly using biotechnology techniques. Recently, biotechnological processes for producing riboflavin have been in ascendance. In riboflavin fermentative production processes, it is extremely difficult to purify and concentrate riboflavin to the extent required for pharmaceutical and foodstuff applications.
For pharmaceutical and foodstuff applications the fermentatively produced riboflavin to be purified is usually first dissolved in an acidic or alkaline solution. Usually, contaminants, such as cell residue, proteins, peptides, and amino acids which may remain in dissolved or undissolved form after the dissolution of the riboflavin can then be separated from the riboflavin only with a relatively large effort by the combination of several different specific operations.
In conventional processes, dissolved riboflavin is usually crystallized out of solution as needle-shaped crystals that normally correspond to its stable modification A form using a variety of procedures, usually at temperatures above 30.degree. C. (see, for example, U.S. Pat. Nos. 2,324,800, 2,797,215 and 4,687,847).
Furthermore, riboflavin has hitherto been produced and marketed exclusively in the stable crystal modification A form. Riboflavin in this form is soluble in water only to a very limited extent. Thus, the solubility behavior of this form of riboflavin is relatively poor for pharmaceutical and foodstuff applications. Accordingly, for a long time, there has existed the need to improve the solubility behavior and the bioavailability of riboflavin.
Various reports in the literature disclose different stable crystal modifications of riboflavin, which are formed by precipitation from an alkaline solution. From such reports, however, no practical operating process has been developed, presumably due to the chemical degradation of riboflavin in alkaline solutions (see, for example, U.S. Pat. No. 2,603,633).
The riboflavin marketed today is partly in the form of very fine powder and partly in the form of long yellow needles. The fine powder form of riboflavin has a considerable dustiness, an extremely low bulk density, and a poor flow behavior. This form of riboflavin also becomes charged very readily. Consequently, pressing the fine powder form of riboflavin into tablets is hindered, and additives are required to improve its flow and compacting behavior.
Likewise, the riboflavin needles exhibit a strong dust generation when processed and are problematic during further processing, such as, for example, in the vitaminization of flour. Also, various agglomeration procedures carried out during the crystallization process have hitherto not been used for the large-scale production of riboflavin (see, for example, Canadian Patent 633,852 and European Patent 307,767). Additional agglomeration procedures are carried out during the drying step using needle-shaped crystals of modification A (German Offenlegungsschrift 4,014,262).
Accordingly, a need continues to exist for a process that produces a form of riboflavin which possesses substantially better physical properties, such as better flow and dissolution properties and abrasive resistance compared to riboflavin produced by conventional processes, and which has a purity (riboflavin content) of above 98%.